4-Arylpiperidines have long been recognized as a valuable class of compounds capable of effecting the central nervous system in animals. Several 4-phenylpiperidines having various substituents attached to the piperidine ring are known. McElvain et al., for example, disclose a number of 1-methyl-4-alkyl-4-arylpiperidines in U.S. Pat. No. 2,892,842. In J. Am. Chem. Soc., 80, 3915-3923 (1958), McElvain et al. reported the preparation of 1,3,4-trimethyl-4-(2-methoxyphenyl)piperidine as a bi-product in the synthesis of a 1,4-dialkyl-4-arylpiperidine. A number of 1,2,3-trialkyl-3-arylpiperidines have been reported as analgesic drugs, see U.S. Pat. Nos. 3,043,845 and 2,892,842. Similarly, various 1-aroyl-3,4-dialkyl-4-arylpiperidines have been reported to be useful as central nervous system depressants, U.S. Pat. No. 3,080,372. It recently has been discovered that not only is an alkyl group located in the piperidine 3-position important for unique biological activity, but also that separation of optical isomers provides compounds displaying narcotic agonist activity and mixed agonist-antagonist activity, see U.S. Pat. No. 4,081,450.
An object of this invention is to provide 4-arylpiperidines which are more highly substituted in the piperidine ring than any of the prior art compounds.